Seminar: Neuropathics for ADHD: Do they work?

Abstract

I will review the evidence for neuroimaging deficits in attention deficit/hyperactivity disorder (ADHD) and of efficacy of neurotherapeutics that target these imaging deficits. ADHD patients have functional deficits in several domain-dependent fronto-striatal, fronto-parietal and fronto-cerebellar networks (Rubia et al., 2021). The frontal parts of these networks in particular have been targeted with neurotherapeutics. EEG-neurofeedback has been tested for about 45 years, with the latest meta-analyses of randomised controlled trials (RCT) showing small/medium effects compared to non-active controls only. Our proof of concept functional magnetic resonance imaging neurofeedback (fMRI-NF) study of right inferior frontal cortex in ADHD adolescents showed significant effects of improving fronto-striatal brain function and connectivity and reducing default mode network connectivity (Alegria et al., 2007, Rubia et al., 2013), which, however, was not replicated in the larger RCT (Lam et al., 2022). Brain stimulation has been applied to ADHD using mostly repetitive transcranial magnetic and direct current stimulation (rTMS/tDCS). rTMS has shown mostly negative findings on improving cognition or symptoms. Meta-analyses of tDCS studies targeting mostly the dorsolateral prefrontal cortex show small effects on cognitive improvements with only two out of three studies showing clinical improvements (Westwood et al., 2021a, Rubia et al., 2021, Rubia 2022). Our largest study targeting rIFC also showed no clinical, cognitive or brain function improvements (Westwood et al., 2021b). Our latest study, however, showed an improvement in attention in adults with ADHD with 4 weeks of 28 sessions of tDCS of right dorsolateral prefrontal cortex, suggesting the need for large number of sessions to show clinical efficacy (Douglas et al). Trigeminal nerve stimulation has been shown to improve ADHD symptoms with medium effect size in one proof of concept RCT. Modern neurotherapeutics are attractive due to their relative safety and potential neuroplastic effects. However, they need to be more thoroughly tested for clinical and cognitive efficacy across settings, protocols and beyond core symptoms and for their potential for individualised treatment.

References

Alegria AA, Wulff M, Brinson H, Barker GJ, Norman LJ, Brandeis D, Stahl D, David AS, Taylor E, Giampietro V, Rubia K. (2017) Real-time fMRI neurofeedback in adolescents with attention deficit hyperactivity disorder. Hum Brain Mapp. 38(6):3190-3209

Lam S-L, Criaud, M, Lukito, S, Westwood S, Agbedjro, D, Kowalczyk, OS, Curran S, Barret N, M.Abbott C, Liang H, Simonoff E, Barker GJ, Giampietro, V, Rubia K (2022).  A double-blind, randomised, sham-controlled trial testing the efficacy of fMRI neurofeedback on clinical and cognitive measures in children with ADHD. American Journal of Psychiatry, in press.

Rubia K (2019) Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its Clinical Translation. Front Hum Neurosci. 12:100

Biography

Katya Rubia is Prof of Cognitive Neuroscience, Deputy Head of Department of Child & Adolescent Psychiatry at the IOPPN, KCL and also a KCL-Dresden Transcampus Professor at Dresden University, Germany.

Prof Rubia is a world-leading expert of MRI neuroimaging of ADHD with over 27 years of expertise. Her work focusses on functional and structural neuroimaging of child psychiatric disorders, most prominently of ADHD but also related disorders such as autism, conduct disorder, obsessive-compulsive disorder and child abuse. Other topics are pharmacological neuroimaging of drugs used in ADHD with fMRI and PET. Her more recent interest is the investigation of neurotherapies such as fMRI-Neurofeedback and non-invasive brain stimulation in children with ADHD. Prof Rubia is also conducting studies on the brain correlates of Meditation.

Prof Rubia has published more than 200 papers in high impact journals, with an h-factor of 98. She was included in the Clarivate 2019 and 2020 as one of the most cited researchers of the past decade. Her research is funded by the Medical Research Council UK (MRC), National Institute of Health Research (NIHR), various charities and industry. She obtained the European Kramer-Pollnow Prize for her contribution to research in child psychiatry in 2013 and is a corresponding foreign member of the Royal National Academy of Medicine of Spain. She is member of several grant review panels like the UK Medical Research Council and of the Editorial boards of several Neuroscience journals including Biological Psychiatry.

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